1. Field of the Invention
The present invention is directed to methods, systems and devices for the characterization of cardiac rhythms and, particularly, characterization of ventricular fibrillation and to methods, systems and devices to be used in the treatment of ventricular fibrillation based upon the characterization of ventricular fibrillation.
References set forth herein may facilitate understanding of the present invention or the background of the present invention. Inclusion of a reference herein is not intended to and does not constitute an admission that the reference is available as prior art with respect to the present invention.
2. Prior Art
Ventricular Fibrillation (VF) is the initial rhythm in 40% of cardiac arrests thereby accounting for approximately 140,000 such events yearly in the U.S. alone. In ventricular fibrillation of short duration, immediate defibrillation is universally accepted as the most effective therapy. This is reflected in the current recommendations for 3 initial shocks when VF is the presenting rhythm. See, for example, American Heart Association in Collaboration with the International Liaison Committee on Resuscitation, “Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: an international consensus on science,” Circulation, 102(8) (Suppl.I):I-136-57 2000, and American Heart Association in Collaboration with the International Liaison Committee on Resuscitation, “International Guidelines 2000 for CPR and ECC: a consensus on science,” Resuscitation, 46(1-3):1-447 2000. When prolonged VF is present, as defined by VF of over 4 minutes duration, there is compelling evidence that CPR prior to defibrillation improves survival. See, Cobb LA, Fahrenbruch C, Walsh T, Copass M, Olsufka M, Breskin M, Hallstrom A. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281 (13): 1182-8; and Wik L, Hansen T B, Fylling F, Steen T, Vaagnes P, Auestad B H, Steen P A. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation. JAMA 2003; 289 (11): 1389-95. In the Seattle study by Cobb et al., patients with ambulance response times of over 4 minutes who received CPR for 90 seconds had an observed survival increase from 17% without CPR to 27% with CPR being given first. In the study by Wik et al. based in the Netherlands, patients with ambulance responses times over 5 minutes who received CPR for 3 minutes prior to defibrillation demonstrated an increased survival from 4% without CPR to 22% with CPR first. Based on these studies, survival from prolonged ventricular fibrillation, defined as VF of over 5 minutes duration could be improved by over 10% if CPR would be provided prior to defibrillation. In order to provide immediate defibrillation to those in the first 5 minutes who have the highest probability of response, while giving those with prolonged VF the benefit of CPR, a quantitative method to estimate VF duration is essential. Since the duration of VF is difficult to determine with accuracy in the field, a reliable method based on the ECG waveform would be very useful.
Waveform analysis has progressed significantly over the past 20 years. Early methods to select patients more likely to respond to defibrillation were based on amplitude and the average (median) frequency of short segments of the signal. See, Weaver W D, Cobb L A, Dennis D, Ray R, Hallstrom A P, Copass M K. Amplitude of ventricular fibrillation waveform and outcome after cardiac arrest. Ann Intern Med 1985; 102 (1): 53-5; and Dzwonczyk R, Brown C G, Werman H A. The median frequency of the ECG during ventricular fibrillation: its use in an algorithm for estimating the duration of cardiac arrest. IEEE Trans Biomed Eng 1990; 37: 640-6. Proposed strategies have sought to insure that those who have VF of less than 5 minutes duration, or would respond to defibrillation with “return of organized rhythm” (ROOR) or “return of spontaneous circulation” (ROSC), would receive an immediate shock at least 95% percent of the time. Using the 95% “cutpoint” (a term meaning a threshold often used with Receiver Operating Characteristic (ROC) curves) for sensing the “TRUE POSITIVES” (i.e. those with VF duration under 5 minutes or with ROOR/ROSC as a response to immediate defibrillation) as the baseline, the focus was then directed at detecting the highest percentage possible of “TRUE NEGATIVES”, that is: those who would not respond to the initial defibrillation attempt and therefore should receive CPR and other therapies to increase survival by the estimated 10-15% as demonstrated in the studies cited above. We note that overall survival may be maximized by lowering the sensitivity for detecting TRUE POSITIVES in order to increase capture of the TRUE NEGATIVES. This will be addressed in detail in the survival benefit analysis portion of this application. While using a 95% cutpoint does not optimize survival, it does serve as a recognized point to be used to compare the various methods of waveform analysis. Using this 95% cutpoint for detecting VF of less than 5 minutes as our comparison point, our data show that amplitude allows only 4%, and median frequency only 51% of prolonged VF to be selected.
Measurement of amplitude has been further refined by considering the fractal dimension of the waveform, a measure termed the scaling exponent (ScE). See, Callaway C W, Sherman L D, Menegazzi J J, Scheatzle M D. Scaling structure of electrocardiographic waveform during prolonged ventricular fibrillation in swine. Pacing Clin Electrophysiol 2000; 2: 180-91; and U.S. Pat. No. 6,438,419, the disclosures of which are incorporated herein by reference. The ScE measures the roughness of the waveform quantitatively by analyzing the signal for self-similarity. The pattern of peaks in the waveform is examined at smaller and smaller scales or magnifications. When there are similar patterns at several decreasing scales, a region of “scaling” is identified. This method works well in the laboratory at recording rates of 1000 samples/second and with no filtering. Using the scaling exponent, 20% of TRUE NEGATIVES, defined as VF of over 5 minutes duration, can be identified when the 95% cutpoint is used for comparison. Unfortunately, when applied to data obtained at recording rates of 125 samples/second and with low pass filtering below 60 Hz characteristic of currently used defibrillators, the scaling regions are no longer seen. This observation motivated our search for a method which would quantitatively measure the features of VF related to amplitude but which could be used in current clinical devices. This method is the Logarithm of the Absolute Correlations, or LAC. See, U.S. Patent Provisional Application Ser. No. 60/521,465, filed Apr. 30, 2004, the disclosure of which is incorporated herein by reference.
The frequency spectrum and frequency based measures have also been exploited. These have focused either on Fourier analysis. See Dzwonczyk, R, et al., “The median frequency of the ECG during ventricular fibrillation: its use in an algorithm for estimating the duration of cardiac arrest,” IEEE Trans Biomed Eng, 37: 6406 1990; Brown, C G and Dzwonszyk, R, “Signal analysis of the human electrocardiogram during ventricular fibrillation: frequency and amplitude parameters as predictors of successful countershock,” Ann Emerg Med, 27(2): 184-8, 1996; Berg, R A, et al., “Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: a randomized, controlled swine study,” Ann Emerg Med,40(6): 563-70, 2002; U.S. Pat. Nos. 5,077,667, 5,957,856 and 6,171,255. Another novel frequency based measure based on chaos theory and “attractor reconstruction” called the “Angular Velocity” (AV) has also been used. See, Sherman L D, Callaway C W, Menegazzi J J. Ventricular fibrillation exhibits dynamical properties and self-similarity. Resuscitation 2000; 47(2): 163-73; and Sherman L D, Flagg A, Callaway C W, Menegazzi J J, Hsieh M. Angular velocity: a new method to improve prediction of ventricular fibrillation duration. Resuscitation 2004; 60: 79-90. In Fourier based methods, the “Median Frequency” is usually employed. The MF is a weighted measure that produces a measure of the ‘center of mass’ of the frequency spectrum when applied to a short segment of VF. It follows a multiphasic pattern which limits its ability to distinguish appropriate phases of VF.
The AV involves reconstruction of a disc-like structure from identical copies of short segments of the VF waveform that are offset by a fixed number of points called the ‘lag’. Since the VF is an irregular wave, the offset copies are out of phase. When each set of 3 points is used as a point in a 3 dimensional plot, the plot is said to be in 3 dimensional “phase space” and a disc shaped structure results. As this disc is formed, the leading edge rotates around a central point. The rate of this rotation was noted to be more rapid in early VF and slower at later time periods. When the number of radians of rotation for each second is averaged, this is a measure termed the Angular Velocity.
The MF and AV follow very similar patterns, although the AV does not rise at later time periods as is seen for the MF. At the 95% cutpoint used for comparison, MF detects 51% and the AV detects 60% of the TRUE NEGATIVES (VF epochs over 5 minutes) demonstrating its improved ability to distinguish these two important phases of VF.
Amplitude and frequency are essentially the only features of the VF waveform that have been correlated with VF duration. Combining two measures of these features (the ScE for amplitude/scaling and the AV for frequency) in a two dimensional model and using a classification line that is based on optimal separation between TRUE POSITIVES at a 95% cutpoint and TRUE NEGATIVES has increased the detection of TRUE NEGATIVES to 65%. See Sherman et al. Resuscitation, 2004;60:79-90 cited above. This method cannot be used in current defibrillators because the recording rates of approximately 120 samples/second and filters (<60 Hz) which are present eliminate the scaling region from which the ScE is calculated. This prompted a search for a method which would function well under these conditions. “Correlations” are a mathematical technique used to estimate the similarity of one signal to another. If the correlation between two signals is high, then there is a large amount of similarity between the signals. Self-similarity of a signal with itself can also be examined. This “autocorrelation” measures how the signal is similar to itself at different points along its length. This differs from the scaling exponent which measures similarity at different magnifications of the signal (i.e. along its height). Study of raw autocorrelations of 5 second intervals of VF showed that large autocorrelations are present in early VF and become smaller with the passage of time. These autocorrelations are deviations above and below the zero baseline. The negative amplitudes can be brought above the zero baseline by taking the absolute values of the correlations. This allows the area under the curve to be summed and for this sum to give a positive result. The logarithm of this sum serves as a measure of the “longitudinal” self-similarity of the waveform. This is termed the “Logarithm of the Absolute Correlations”, or LAC. The formula for the LAC being:LAC=Log10(Σk(|Σi(X(i)·X(i+N))|)); {k from 1 to N, i from 1 to n−N}.
With a suitable mathematical transformation depending on recording rates, the LAC may be converted to values that closely match the ScE in magnitude. This transformation is called the “LACadjusted”. This feature indicates that the self-similarity measured by the fractal dimension (ScE) in the sense of magnification can be closely approximated by the self-similarity measured by the LAC in the longitudinal sense. Of course, for VF they can only be compared at high sampling rates because the ScE does not produce useful information at sampling rates below 250 Hz or when the signal is filtered below about 125 Hz.
While this historical review demonstrates that progress has been made in developing methods for determining the duration of ventricular fibrillation and likelihood of successful defibrillation, it remains desirable to develop improved devices and methods for determining the duration of ventricular fibrillation as well as improved treatment devices, systems, methods and protocols for treatment of ventricular fibrillation based on these. We therefore endeavored to improve the frequency based measures for analyzing VF as follows.